Areas of research
Myeloma functional heterogeneity in clinical drug resistance and residual disease
Myeloma heterogeneity is the single most important obstacle for optimal therapeutic targeting. A complex genetic landscape, epigenetic mechanisms and cues from tumour microenvironments shape the phenotypic and functional diversification of myeloma cells, which underpins drug resistance and later relapsed disease. Differential transcriptional profiles and gene expression regulatory mechanisms at diagnosis and residual disease provide insight into the biology of drug resistance and reveal novel disease vulnerabilities.
The lab is particularly interested in the biology of BCL2 family proteins. BCL2 inhibition is a promising targeted therapy for t(11;14) myeloma and a unique paradigm of treatment directed by genetics.
Myeloma kidney disease and MGRS
Myeloma kidney disease is a debilitating complication with a profound impact on treatment outcome and survival. Monoclonal Gammopathy of Renal Significance (MGRS) is a rare disease, where small amounts of highly nephrotoxic immunoglobulins or free light chains, produced by otherwise subclinical plasma cell clones, resulting in a bewildering array of renal histopathology and kidney disease.
The lab collaborates with Renal Medicine and Histopathology at Imperial to establish experimental vitro and vivo models of myeloma cast nephropathy and MGRS. We study the proinflammatory and profibrotic pathways induced by the nephrotoxic immunoglobulins and develop novel diagnostics and therapeutic strategies.